Placental stem cell populations

• US 20070275362A1
• Filed: 12/28/2006
• Published: 11/29/2007
• Est. Priority Date: 12/06/2000
• Status: Active Grant

• Current Assignee: Celularity, Inc.
• Original Assignee: Anthrogenesis Corporation (Bristol-Myers Squibb Company)
• Inventors: Ye, Qian, Wang, Jia-Lun, Edinger, James, Hariri, Robert
• Granted Patent: US 8,057,788 B2
• Time in Patent Office: Days
• US Class Current: 435/1.200
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 35/644 Beeswax; Propolis; Royal jelly; Honey
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 2500/25 Insulin-transferrin; Insulin-transferrin-selenium
• CPC Class Codes: C12N 2500/36 Lipids
• CPC Class Codes: C12N 2500/42 Organic phosphate, e.g. beta glycerophosphate
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/135 Platelet-derived growth factor [PDGF]
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2533/52 Fibronectin; Laminin
• CPC Class Codes: C12N 5/0605 : Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/0607 : Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696

Abstract

The present invention provides placental stem cells and placental stem cell populations, and methods of culturing, proliferating and expanding the same. The invention also provides methods of differentiating the placental stem cells. The invention further provides methods of using the placental stem cells in assays and for transplanting.

Claims

1. An isolated adherent placental stem cell that is:

CD200⁺ and HLA-G⁺;

CD73⁺, CD105⁺, and CD200⁺;

CD200⁺ and OCT-4⁺;

CD73⁺, CD105⁺ and HLA-G⁺;

CD73⁺ and CD105⁺ and facilitates the formation of one or more embryoid-like bodies in a population of placental cells comprising said stem cell when said population is cultured under conditions that allow the formation of an embryoid-like body;

or

OCT-4⁺ and facilitates the formation of one or more embryoid-like bodies in a population of placental cells comprising the stem cell when said population is cultured under conditions that allow formation of embryoid-like bodies;

or any combination thereof.

2. The isolated stem cell of claim 1, wherein said CD200⁺, HLA-G⁺ stem cell is CD34⁻

, CD38⁻

, CD45⁻

, CD73⁺ and CD105⁺.

3. The isolated stem cell of claim 1, wherein said CD73⁺, CD105⁺, and CD200⁺ stem cell is CD34⁻

, CD38⁻

, CD45⁻

, and HLA-G⁺.

4. The isolated stem cell of claim 1, wherein said CD200⁺, OCT-4⁺ stem cell is CD34⁻

, CD38⁻

, CD45⁻

, CD73⁺, CD105⁺ and HLA-G⁺.

5. The isolated stem cell of claim 1, wherein said CD73⁺, CD105⁺ and HLA-G⁺ stem cell is CD34⁻

, CD45⁻

, OCT-4⁺ and CD200⁺.

6. The isolated stem cell of claim 1, wherein said CD73⁺ and CD105⁺ stem cell that facilitates the formation of one or more embryoid-like bodies is OCT4⁺, CD34⁻

, CD38⁻

and CD45⁻

.

7. The isolated stem cell of claim 1, wherein said OCT-4⁺ and which facilitates the formation of one or more embryoid-like bodies is CD73⁺, CD105⁺, CD200⁺, CD34⁻

, CD38⁻

, and CD45⁻

.

31. The isolated stem cell of claim 1, wherein said stem cell expresses one or more genes at a detectably higher level than a bone marrow-derived mesenchymal stem cell,

wherein said one or more genes are selected from the group consisting of ACTG2, ADARB1, AMIGO2, ARTS-1, B4GALT6, BCHE, C11orf9, CD200, COL4A1, COL4A2, CPA4, DMD, DSC3, DSG2, ELOVL2, F2RL1, FLJ10781, GATA6, GPR126, GPRC5B, ICAM1, IER3, IGFBP7, IL1A, IL6, IL18, KRT18, KRT8, LIPG, LRAP, MATN2, MEST, NFE2L3, NUAK1, PCDH7, PDLIM3, PKP2, RTN1, SERPINB9, ST3GAL6, ST6GALNAC5, SLC12A8, TCF21, TGFB2, VTN, and ZC3H12A, and

wherein said bone marrow-derived stem cell has undergone a number of passages in culture that is equivalent to the number of passages said placental stem cell has undergone.

34. A composition comprising the isolated stem cell of claim 1.

36. The composition of claim 34 that comprises about 1.25% w/v human serum albumin and about 2.5% w/v dextran.

38. The composition of claim 34 comprising a matrix.

43. The composition of claim 38, wherein said matrix comprises an extracellular membrane protein.

44. The composition of claim 38, wherein said matrix comprises a synthetic compound.

45. The composition of claim 38, wherein said matrix comprises a bioactive compound.

46. The composition of claim 44, wherein said bioactive compound is a growth factor, cytokine, antibody, or organic molecule of less than 5,000 daltons.

47. The composition of claim 38, wherein a plurality of said stem cells expresses one or more genes at a detectably higher level than a bone marrow-derived mesenchymal stem cell,

said one or more genes are selected from the group consisting of ACTG2, ADARB1, AMIGO2, ARTS-1, B4GALT6, BCHE, C11orf9, CD200, COL4A1, COL4A2, CPA4, DMD, DSC3, DSG2, ELOVL2, F2RL1, FLJ10781, GATA6, GPR126, GPRC5B, ICAM1, IER3, IGFBP7, IL1A, IL6, IL18, KRT18, KRT8, LIPG, LRAP, MATN2, MEST, NFE2L3, NUAK1, PCDH7, PDLIM3, PKP2, RTN1, SERPINB9, ST3GAL6, ST6GALNAC5, SLC12A8, TCF21, TGFB2, VTN, and ZC3H12A, and

wherein said bone marrow derived stem cell has undergone a number of passages in culture equivalent to a number of passages for said placental stem cell.

48. The composition of claim 47, wherein said stem cells express ACTG2, ADARB1, AMIGO2, ARTS-1, B4GALT6, BCHE, C11orf9, CD200, COL4A1, COL4A2, CPA4, DMD, DSC3, DSG2, ELOVL2, F2RL1, FLJ10781, GATA6, GPR126, GPRC5B, ICAM1, IER3, IGFBP7, IL1A, IL6, IL18, KRT18, KRT8, LIPG, LRAP, MATN2, MEST, NFE2L3, NUAK1, PCDH7, PDLIM3, PKP2, RTN1, SERPINB9, ST3GAL6, ST6GALNAC5, SLC12A8, TCF21, TGFB2, VTN, and ZC3H12A at a detectably higher level than a population of isolated bone marrow-derived mesenchymal stem cell.

49. A method of producing cartilaginous tissue comprising culturing a plurality of the stem cell of claim 1 under conditions in which said stem cell differentiates into a chondrocytic cell, said culturing being for a time sufficient for said chondrocytic cell to produce a detectable amount of glygosaminoglycans and collagen.

50. A composition comprising the isolated placental stem cell of claim 1, and a compound that induces the differentiation of said stem cell into a chondrocytic cell, an adipocytic cell, a neuronal cell, an osteocytic cell, a pancreatic cell or a cardiac cell.

8. A population of isolated placental stem cells that is enriched for adherent placental stem cells that are:

CD200⁺ and HLA-G⁺;

CD73⁺, CD105⁺, and CD200⁺;

CD200⁺ and OCT-4⁺;

CD73⁺, CD105⁺ and HLA-G⁺;

CD73⁺ and CD105⁺ and facilitate the formation of one or more embryoid-like bodies in a population of placental cells comprising said stem cell when said population is cultured under conditions that allow the formation of an embryoid-like body;

or

OCT-4⁺ and facilitate the formation of one or more embryoid-like bodies in a population of placental cells comprising the stem cell when said population is cultured under conditions that allow formation of embryoid-like bodies.

9. The population of claim 8, wherein said CD200⁺, HLA-G⁺ stem cells are CD34⁻

, CD38⁻

, CD45⁻

, CD73⁺ and CD105⁺.

10. The population of claim 8, wherein said CD73⁺, CD105⁺, and CD200⁺ stem cells are CD34⁻

, CD38⁻

, CD45⁻

, and HLA-G⁺.

11. The population of claim 8, wherein said CD200⁺, OCT-4⁺ stem cell is CD34⁻

, CD38⁻

, CD45⁻

, CD73⁺, CD105⁺ and HLA-G⁺.

12. The population of claim 8, wherein said CD73⁺, CD105⁺ and HLA-G⁺ stem cells are CD34⁻

, CD45⁻

, OCT-4⁺ and CD200⁺.

13. The population of claim 8, wherein said CD73⁺ and CD105⁺ stem cells that facilitate the formation of one or more embryoid-like bodies are OCT4⁺, CD34⁻

, CD38⁻

and CD45⁻

.

14. The population of claim 8, wherein said OCT-4⁺ stem cells that facilitate the formation of one or more embryoid-like bodies are CD73⁺, CD105⁺, CD200⁺, CD34⁻

, CD38⁻

, and CD45⁻

.

15. The population of claim 8, wherein said population has been expanded.

16. The population of claim 8, wherein said population has been passaged at least once.

17. The population of claim 8, wherein said population has been passaged at least three times.

18. The population of claim 8, wherein said population has been passaged at least five times.

19. The population of claim 8, wherein said population has been passaged at least ten times.

20. The population of claim 8, wherein said cells have been cryopreserved, and wherein said population is contained within a container.

21. The population of claim 8, wherein said container is a bag suitable for the intravenous delivery of a liquid.

22. The population of claim 8, wherein said population comprises 1×

10⁶ said stem cells.

23. The population of claim 8, wherein said population comprises 1×

10⁷ said stem cells.

24. The population of claim 8, wherein said population comprises 1×

10⁸ said stem cells.

25. The population of claim 8, wherein said population comprises 1×

10⁹ said stem cells.

26. The population of claim 8, wherein said population comprises 1×

10¹⁰ said stem cells.

27. The population of claim 8, wherein said stem cells have been passaged no more than 5 times.

28. The population of claim 8, wherein said stem cells have been passaged no more than 10 times.

29. The population of claim 8, wherein said stem cells have been passaged no more than 20 times.

30. The population of claim 8, wherein said population is contained in a 0.9% NaCl solution.

32. The population of isolated stem cells of claim 8, wherein a plurality of said stem cells express one or more genes at a detectably higher level than a population of bone marrow-derived mesenchymal stem cells,

wherein said one or more genes are selected from the group consisting of ACTG2, ADARB1, AMIGO2, ARTS-1, B4GALT6, BCHE, C11orf9, CD200, COL4A1, COL4A2, CPA4, DMD, DSC3, DSG2, ELOVL2, F2RL1, FLJ10781, GATA6, GPR126, GPRC5B, ICAM1, IER3, IGFBP7, IL1A, IL6, IL18, KRT18, KRT8, LIPG, LRAP, MATN2, MEST, NFE2L3, NUAK1, PCDH7, PDLIM3, PKP2, RTN1, SERPINB9, ST3GAL6, ST6GALNAC5, SLC12A8, TCF21, TGFB2, VTN, and ZC3H12A, and

wherein said bone marrow derived stem cell has undergone a number of passages in culture that is equivalent to the number of passages said placental stem cell has undergone, and

wherein said population of bone marrow-derived mesenchymal stem cells has a number of cells equivalent to that in said population of isolated stem cells.

33. The population of isolated stem cells of claim 32, wherein said stem cells express ACTG2, ADARB1, AMIGO2, ARTS-1, B4GALT6, BCHE, C11orf9, CD200, COL4A1, COL4A2, CPA4, DMD, DSC3, DSG2, ELOVL2, F2RL1, FLJ10781, GATA6, GPR126, GPRC5B, ICAM1, IER3, IGFBP7, IL1A, IL6, IL18, KRT18, KRT8, LIPG, LRAP, MATN2, MEST, NFE2L3, NUAK1, PCDH7, PDLIM3, PKP2, RTN1, SERPINB9, ST3GAL6, ST6GALNAC5, SLC12A8, TCF21, TGFB2, VTN, and ZC3H12A at a detectably higher level than a population of isolated bone marrow-derived mesenchymal stem cell.

35. A composition comprising the population of claim 8.

37. The composition of claim 35 that comprises about 1.25% w/v human serum albumin and about 2.5% w/v dextran.

39. The composition of claim 35 comprising a matrix.

40. The composition of claim 39, wherein said matrix is a three-dimensional scaffold.

41. The composition of claim 39, wherein said matrix comprises collagen, gelatin, laminin, fibronectin, pectin, ornithine, or vitronectin.

42. The composition of claim 39 wherein said matrix is an amniotic membrane or amniotic membrane-derived biomaterial.

51. A composition comprising the population of isolated stem cells of claim 8, and a compound that induces the differentiation of a plurality of stem cells in said population of stem cells into chondrocytic cells, adipocytic cells, neuronal cells, osteocytic cells, pancreatic cells or cardiac cells.

52. A composition comprising a population of isolated placental stem cells collected by perfusion, wherein said composition comprises at least a portion of the perfusion solution used to collect the placental stem cells.